The first trial will involve the generation of donor alloantigen-specific CD4+CD25+ Tregs from peripheral blood of pre-transplant patients, the administration of the CD4+CD25+ Tregs (1 x 106 cells/kg) at several intervals (for graft specific tolerance induction).

The first trial will involve the generation of CD4+CD25+CD127- Tregs from peripheral blood of pre-transplant patients, followed by a course (up to 24 months) of tacrolimus (5-10 ng/ml) treatment (to prevent chronic rejection) and the administration of the CD4+CD25+CD127- Tregs (1 x 106 cells/kg) at several intervals (for tolerance induction). The immunesuppress drugs will be gradully withdraw within one year. The number of CD4+CD25+ Tregs needed is based on the assumption that the frequencies of alloreactive CD4+ T cells with direct and indirect allospecificity were 1/104 and 1/105, respectively.

The second trial will be carried out in 1-10 year post living donor liver transplantation patients currently under immunosuppressive drug treatment. The investigators will isolate CD4+CD25+CD127- Tregs from these patients, and expand them with mismatched living donor antigens. The patients will be subsequently treated with the expanded donor-antigen specific CD4+CD25+CD127- Tregs (1 x 106 cells/kg) at several intervals, and immunosuppressive drug treatment will be withdrawn.

In both clinical trials, the investigators will monitor the number of allospecific Tregs in patients at different time periods, and to test their suppressive functions in vitro. If there will be any signs of graft rejection, patients will be switched back to immunosuppressive drug treatment. The investigators expect that the innovative Tregs immunosuppressive regimen will lead to achieve permanent liver transplantation tolerance without the use of conventional immunosuppressive drugs: the holygrail in clinical transplantation medicine.

Eligibility

Ages Eligible for Study:

10 Years to 60 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Weight greater than 50kg

Will be receiving a living-related primary liver allograft

Negative B-cell and T-cell cytotoxic and flow cytometry crossmatch

Normal echocardiogram (ECG) with an ejection fraction of greater than 50%

Parents willing to comply with the study visits

Exclusion Criteria:

Current active infection

Pregnant or breastfeeding

Evidence of HIV infection or known HIV positive serology

Antibody positive for hepatitis C virus

Surface antigen positive for HBV

Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB (positive Mantoux test)

Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant

Currently receiving any immunosuppressive agent

Anticipated contraindication to taking medications orally or via nasogastric tube by the morning of Day 2 following completion of the transplant procedure

Require certain medications

Known hypersensitivity to any of the study medications,

Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study

Anticipated contraindication to study medications administration for longer than 5 days post-transplant

History of rejection after organ transplantation

Muti-organ transplantation

Autoimmune disease

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624077

Locations

China, Jiangsu

Nanjing Medical University

Nanjing, Jiangsu, China, 210029

Sponsors and Collaborators

Nanjing Medical University

University of Minnesota - Clinical and Translational Science Institute